1. The Field of the Invention
This invention relates generally to a method whereby optical scattering in a turbid medium may be reduced by photo-bleaching of substances which contribute to inhomogeneities in the index of refraction within the medium.
2. Background and Relevant Art
In many significant applications, a sample is illuminated with light, and information related to the composition of the sample is ascertained from transmitted, reflected, elastically scattered radiation, and/or inelastically scattered radiation. If it is desired to determine the concentration of substances which are deeply embedded in the sample, the presence of excessive elastic scattering can present insuperable difficulties. In such circumstances, the incident radiation will spread out in the sample, losing intensity in the process. In addition, light originating in the sample from inelastic processes such as fluorescence or Raman scattering will spread out from the point of origin, losing intensity upon transiting the turbid medium prior to exiting at the surface.
The aforementioned phenomenon of excessive scattering gives rise to practical problems in spectroscopy. In particular, the spreading of the radiation makes it necessary to image a source of significantly greater radial dimension than would be necessary in the absence of scattering, in order to collect a larger fraction of the desired radiation. For collecting optics of fixed focal length, there will be a spread in the angular distribution of the collected radiation which is proportional to the radial dimension of the spot being imaged. It is fundamental to many methods of wavelength discrimination that differing wavelengths incident at the same angle, cannot be distinguished from the same wavelengths incident at differing angles. The apparatus is incapable of distinguishing angular deviations from wavelength deviations. In consequence, a large spread in angles incident on the spectrometer reduces the resolution of the instrument accordingly.
Alternatively, to maintain spectral resolution, one could choose to increase the focal length of the collecting optics to limit the spread of angles, however, if one wants to preserve the collection efficiency, the diameter of the optics must be scaled up accordingly. It can be readily shown that the optics in the spectroscopic instrument must also be expanded proportionally. Hence, the size and cost of the whole system rises.
In yet another approach to this problem, one may divide up the field of view into multiple bins, each having a smaller spread in angle, and illuminate multiple spectrometers with a multiplicity of such beams. Again, the size and cost of the system will accordingly rise in proportion to the number of such bins.
The problem is particularly important in circumstances where the scattering process of interest is relatively weak in relation to the unwanted elastic scattering. An example of such a case is with Raman scattering which can be used to excite vibrational oscillations of molecules, which scattering spectra can then be used to ascertain the concentration of analytes of interest. Raman scattering is an exceptionally weak process. To obtain good signal to noise ratio in reasonable acquisition times, it is highly desirable to collect as much of the scattered radiation as possible. Yet it is not desirable to substantially degrade the resolution of the spectroscopic equipment. This is particularly important when there is a large broadband background of unwanted radiation, as is often the case where fluorescence from the sample is much larger than the Raman spectra of interest.
An excellent illustration of the problem may occur with biological samples such as human skin. Analytes of interest may primarily reside at some significant depth. As an example, if it is desired to noninvasively analyze the concentration of substances in blood, it is useful to use blood vessels of substantial diameter, but such vessels reside at depths of the order of 2 mm in most places. On the other hand, very substantial scattering generally transpires at depths significantly smaller than 2 mm. Radiation which is targeted at the blood vessel will suffer scattering in penetrating down to the vessel, and the desired scattered radiation from the blood will suffer further scattering prior to its emergence from the skin. To efficiently collect the radiation, it may be necessary to image an area with radius of the order of 1-2 mm. If good wavelength resolution is desired, such as of the order of 1 nm, and if good angular collection efficiency is further desired (such as of the order of f/1.4), it may be necessary to use optics that are several inches in diameter. Such optics are particularly unsuitable to situations where the device is desired to be portable, or worn by the subject.